Molecular Epidemiology of Candida auris in Colombia Reveals a Highly Related, Countrywide Colonization With Regional Patterns in Amphotericin B Resistance

ABSTRACT: Background: Candida auris is a multidrug-resistant yeast associated with hospital outbreaks worldwide. During 2015-2016, multiple outbreaks were reported in Colombia. We aimed to understand the extent of contamination in healthcare settings and to characterize the molecular epidemiology of...

Full description

Autores:
Misas Rivas, Elizabeth
Chow, Nancy A.
Cáceres, Diego H.
Gade, Lalitha
Berkow, Elizabeth L.
Armstrong, Paige
Rivera, Sandra
Escandón, Patricia
Duarte, Carolina
Moulton Meissner, Heather
Welsh, Rory R.
Parra, Claudia
Pescador, Luz Ángela
Villalobos, Nohora
Salcedo, Soraya
BerrÍo, Indira
Varón, Carmen
Espinosa Bode, Andrés
Lockhart, Shawn R.
Jackson, Brendan R.
Litvintseva, Anastasia P.
Beltrán, Mauricio
Chiller, Tom M.
Tipo de recurso:
Article of investigation
Fecha de publicación:
2019
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/39582
Acceso en línea:
https://hdl.handle.net/10495/39582
Palabra clave:
Anfotericina B
Amphotericin B
Farmacología
Pharmacology
Agentes Antifúngicos
Antifungal Agents
Candida
Candida
Candidiasis
Candidiasis
Epidemiología
Epidemiology
Farmacorresistencia Fúngica
Drug Resistance, Fungal
Microbiología Ambiental
Environmental Microbiology
Pruebas de Sensibilidad Microbiana
Microbial Sensitivity Tests
Epidemiología Molecular
Molecular Epidemiology
Tipificación Molecular
Molecular Typing
Técnicas de Tipificación Micológica
Mycological Typing Techniques
Secuenciación Completa del Genoma
Whole Genome Sequencing
https://id.nlm.nih.gov/mesh/D000666
https://id.nlm.nih.gov/mesh/D010600
https://id.nlm.nih.gov/mesh/D000935
https://id.nlm.nih.gov/mesh/D002175
https://id.nlm.nih.gov/mesh/D002177
https://id.nlm.nih.gov/mesh/D004813
https://id.nlm.nih.gov/mesh/D025141
https://id.nlm.nih.gov/mesh/D004783
https://id.nlm.nih.gov/mesh/D008826
https://id.nlm.nih.gov/mesh/D017720
https://id.nlm.nih.gov/mesh/D058889
https://id.nlm.nih.gov/mesh/D016533
https://id.nlm.nih.gov/mesh/D000073336
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc-nd/2.5/co/
id UDEA2_dc21c5184ce35c2f88e4a266c8db28e5
oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/39582
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv Molecular Epidemiology of Candida auris in Colombia Reveals a Highly Related, Countrywide Colonization With Regional Patterns in Amphotericin B Resistance
title Molecular Epidemiology of Candida auris in Colombia Reveals a Highly Related, Countrywide Colonization With Regional Patterns in Amphotericin B Resistance
spellingShingle Molecular Epidemiology of Candida auris in Colombia Reveals a Highly Related, Countrywide Colonization With Regional Patterns in Amphotericin B Resistance
Anfotericina B
Amphotericin B
Farmacología
Pharmacology
Agentes Antifúngicos
Antifungal Agents
Candida
Candida
Candidiasis
Candidiasis
Epidemiología
Epidemiology
Farmacorresistencia Fúngica
Drug Resistance, Fungal
Microbiología Ambiental
Environmental Microbiology
Pruebas de Sensibilidad Microbiana
Microbial Sensitivity Tests
Epidemiología Molecular
Molecular Epidemiology
Tipificación Molecular
Molecular Typing
Técnicas de Tipificación Micológica
Mycological Typing Techniques
Secuenciación Completa del Genoma
Whole Genome Sequencing
https://id.nlm.nih.gov/mesh/D000666
https://id.nlm.nih.gov/mesh/D010600
https://id.nlm.nih.gov/mesh/D000935
https://id.nlm.nih.gov/mesh/D002175
https://id.nlm.nih.gov/mesh/D002177
https://id.nlm.nih.gov/mesh/D004813
https://id.nlm.nih.gov/mesh/D025141
https://id.nlm.nih.gov/mesh/D004783
https://id.nlm.nih.gov/mesh/D008826
https://id.nlm.nih.gov/mesh/D017720
https://id.nlm.nih.gov/mesh/D058889
https://id.nlm.nih.gov/mesh/D016533
https://id.nlm.nih.gov/mesh/D000073336
title_short Molecular Epidemiology of Candida auris in Colombia Reveals a Highly Related, Countrywide Colonization With Regional Patterns in Amphotericin B Resistance
title_full Molecular Epidemiology of Candida auris in Colombia Reveals a Highly Related, Countrywide Colonization With Regional Patterns in Amphotericin B Resistance
title_fullStr Molecular Epidemiology of Candida auris in Colombia Reveals a Highly Related, Countrywide Colonization With Regional Patterns in Amphotericin B Resistance
title_full_unstemmed Molecular Epidemiology of Candida auris in Colombia Reveals a Highly Related, Countrywide Colonization With Regional Patterns in Amphotericin B Resistance
title_sort Molecular Epidemiology of Candida auris in Colombia Reveals a Highly Related, Countrywide Colonization With Regional Patterns in Amphotericin B Resistance
dc.creator.fl_str_mv Misas Rivas, Elizabeth
Chow, Nancy A.
Cáceres, Diego H.
Gade, Lalitha
Berkow, Elizabeth L.
Armstrong, Paige
Rivera, Sandra
Escandón, Patricia
Duarte, Carolina
Moulton Meissner, Heather
Welsh, Rory R.
Parra, Claudia
Pescador, Luz Ángela
Villalobos, Nohora
Salcedo, Soraya
BerrÍo, Indira
Varón, Carmen
Espinosa Bode, Andrés
Lockhart, Shawn R.
Jackson, Brendan R.
Litvintseva, Anastasia P.
Beltrán, Mauricio
Chiller, Tom M.
dc.contributor.author.none.fl_str_mv Misas Rivas, Elizabeth
Chow, Nancy A.
Cáceres, Diego H.
Gade, Lalitha
Berkow, Elizabeth L.
Armstrong, Paige
Rivera, Sandra
Escandón, Patricia
Duarte, Carolina
Moulton Meissner, Heather
Welsh, Rory R.
Parra, Claudia
Pescador, Luz Ángela
Villalobos, Nohora
Salcedo, Soraya
BerrÍo, Indira
Varón, Carmen
Espinosa Bode, Andrés
Lockhart, Shawn R.
Jackson, Brendan R.
Litvintseva, Anastasia P.
Beltrán, Mauricio
Chiller, Tom M.
dc.contributor.researchgroup.spa.fl_str_mv Biología Celular y Molecular CIB U. de A. U. del Rosario
dc.subject.decs.none.fl_str_mv Anfotericina B
Amphotericin B
Farmacología
Pharmacology
Agentes Antifúngicos
Antifungal Agents
Candida
Candida
Candidiasis
Candidiasis
Epidemiología
Epidemiology
Farmacorresistencia Fúngica
Drug Resistance, Fungal
Microbiología Ambiental
Environmental Microbiology
Pruebas de Sensibilidad Microbiana
Microbial Sensitivity Tests
Epidemiología Molecular
Molecular Epidemiology
Tipificación Molecular
Molecular Typing
Técnicas de Tipificación Micológica
Mycological Typing Techniques
Secuenciación Completa del Genoma
Whole Genome Sequencing
topic Anfotericina B
Amphotericin B
Farmacología
Pharmacology
Agentes Antifúngicos
Antifungal Agents
Candida
Candida
Candidiasis
Candidiasis
Epidemiología
Epidemiology
Farmacorresistencia Fúngica
Drug Resistance, Fungal
Microbiología Ambiental
Environmental Microbiology
Pruebas de Sensibilidad Microbiana
Microbial Sensitivity Tests
Epidemiología Molecular
Molecular Epidemiology
Tipificación Molecular
Molecular Typing
Técnicas de Tipificación Micológica
Mycological Typing Techniques
Secuenciación Completa del Genoma
Whole Genome Sequencing
https://id.nlm.nih.gov/mesh/D000666
https://id.nlm.nih.gov/mesh/D010600
https://id.nlm.nih.gov/mesh/D000935
https://id.nlm.nih.gov/mesh/D002175
https://id.nlm.nih.gov/mesh/D002177
https://id.nlm.nih.gov/mesh/D004813
https://id.nlm.nih.gov/mesh/D025141
https://id.nlm.nih.gov/mesh/D004783
https://id.nlm.nih.gov/mesh/D008826
https://id.nlm.nih.gov/mesh/D017720
https://id.nlm.nih.gov/mesh/D058889
https://id.nlm.nih.gov/mesh/D016533
https://id.nlm.nih.gov/mesh/D000073336
dc.subject.meshuri.none.fl_str_mv https://id.nlm.nih.gov/mesh/D000666
https://id.nlm.nih.gov/mesh/D010600
https://id.nlm.nih.gov/mesh/D000935
https://id.nlm.nih.gov/mesh/D002175
https://id.nlm.nih.gov/mesh/D002177
https://id.nlm.nih.gov/mesh/D004813
https://id.nlm.nih.gov/mesh/D025141
https://id.nlm.nih.gov/mesh/D004783
https://id.nlm.nih.gov/mesh/D008826
https://id.nlm.nih.gov/mesh/D017720
https://id.nlm.nih.gov/mesh/D058889
https://id.nlm.nih.gov/mesh/D016533
https://id.nlm.nih.gov/mesh/D000073336
description ABSTRACT: Background: Candida auris is a multidrug-resistant yeast associated with hospital outbreaks worldwide. During 2015-2016, multiple outbreaks were reported in Colombia. We aimed to understand the extent of contamination in healthcare settings and to characterize the molecular epidemiology of C. auris in Colombia. Methods: We sampled patients, patient contacts, healthcare workers, and the environment in 4 hospitals with recent C. auris outbreaks. Using standardized protocols, people were swabbed at different body sites. Patient and procedure rooms were sectioned into 4 zones and surfaces were swabbed. We performed whole-genome sequencing (WGS) and antifungal susceptibility testing (AFST) on all isolates. Results: Seven of the 17 (41%) people swabbed were found to be colonized. Candida auris was isolated from 37 of 322 (11%) environmental samples. These were collected from a variety of items in all 4 zones. WGS and AFST revealed that although isolates were similar throughout the country, isolates from the northern region were genetically distinct and more resistant to amphotericin B (AmB) than the isolates from central Colombia. Four novel nonsynonymous mutations were found to be significantly associated with AmB resistance. Conclusions: Our results show that extensive C. auris contamination can occur and highlight the importance of adherence to appropriate infection control practices and disinfection strategies. Observed genetic diversity supports healthcare transmission and a recent expansion of C. auris within Colombia with divergent AmB susceptibility.
publishDate 2019
dc.date.issued.none.fl_str_mv 2019
dc.date.accessioned.none.fl_str_mv 2024-06-03T13:11:59Z
dc.date.available.none.fl_str_mv 2024-06-03T13:11:59Z
dc.type.spa.fl_str_mv Artículo de investigación
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.redcol.spa.fl_str_mv https://purl.org/redcol/resource_type/ART
dc.type.coarversion.spa.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/article
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/publishedVersion
format http://purl.org/coar/resource_type/c_2df8fbb1
status_str publishedVersion
dc.identifier.issn.none.fl_str_mv 1058-4838
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10495/39582
dc.identifier.doi.none.fl_str_mv 10.1093/cid/ciy411
dc.identifier.eissn.none.fl_str_mv 1537-6591
identifier_str_mv 1058-4838
10.1093/cid/ciy411
1537-6591
url https://hdl.handle.net/10495/39582
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartofjournalabbrev.spa.fl_str_mv Clin. Infect. Dis.
dc.relation.citationendpage.spa.fl_str_mv 21
dc.relation.citationissue.spa.fl_str_mv 1
dc.relation.citationstartpage.spa.fl_str_mv 15
dc.relation.citationvolume.spa.fl_str_mv 68
dc.relation.ispartofjournal.spa.fl_str_mv Clinical Infectious Diseases
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/2.5/co/
dc.rights.uri.spa.fl_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.accessrights.spa.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.coar.spa.fl_str_mv http://purl.org/coar/access_right/c_abf2
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/2.5/co/
https://creativecommons.org/licenses/by-nc-nd/4.0/
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.extent.spa.fl_str_mv 7 páginas
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Oxford University Press
dc.publisher.place.spa.fl_str_mv Chicago, Estados Unidos
institution Universidad de Antioquia
bitstream.url.fl_str_mv https://bibliotecadigital.udea.edu.co/bitstreams/52f79abf-a037-4f6f-a7c6-c455f3743571/download
https://bibliotecadigital.udea.edu.co/bitstreams/397883d4-1672-40d7-a20c-7f7113f303fc/download
https://bibliotecadigital.udea.edu.co/bitstreams/1ad55e44-84b8-4097-ac8f-4c784980a688/download
https://bibliotecadigital.udea.edu.co/bitstreams/b0fc568c-af4c-4eb8-af27-847c6a6eea3e/download
https://bibliotecadigital.udea.edu.co/bitstreams/53a41756-6dac-4f5a-ac6d-9d26538f114d/download
bitstream.checksum.fl_str_mv 9a30edb9d33f6570d97ffe8cef412c88
b88b088d9957e670ce3b3fbe2eedbc13
8a4605be74aa9ea9d79846c1fba20a33
b8804eae3e680a114d2fb7a09a884458
6025f8aade7cc4cd84aa75c3aabd9636
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional de la Universidad de Antioquia
repository.mail.fl_str_mv aplicacionbibliotecadigitalbiblioteca@udea.edu.co
_version_ 1851052531242762240
spelling Misas Rivas, ElizabethChow, Nancy A.Cáceres, Diego H.Gade, LalithaBerkow, Elizabeth L.Armstrong, PaigeRivera, SandraEscandón, PatriciaDuarte, CarolinaMoulton Meissner, HeatherWelsh, Rory R.Parra, ClaudiaPescador, Luz ÁngelaVillalobos, NohoraSalcedo, SorayaBerrÍo, IndiraVarón, CarmenEspinosa Bode, AndrésLockhart, Shawn R.Jackson, Brendan R.Litvintseva, Anastasia P.Beltrán, MauricioChiller, Tom M.Biología Celular y Molecular CIB U. de A. U. del Rosario2024-06-03T13:11:59Z2024-06-03T13:11:59Z20191058-4838https://hdl.handle.net/10495/3958210.1093/cid/ciy4111537-6591ABSTRACT: Background: Candida auris is a multidrug-resistant yeast associated with hospital outbreaks worldwide. During 2015-2016, multiple outbreaks were reported in Colombia. We aimed to understand the extent of contamination in healthcare settings and to characterize the molecular epidemiology of C. auris in Colombia. Methods: We sampled patients, patient contacts, healthcare workers, and the environment in 4 hospitals with recent C. auris outbreaks. Using standardized protocols, people were swabbed at different body sites. Patient and procedure rooms were sectioned into 4 zones and surfaces were swabbed. We performed whole-genome sequencing (WGS) and antifungal susceptibility testing (AFST) on all isolates. Results: Seven of the 17 (41%) people swabbed were found to be colonized. Candida auris was isolated from 37 of 322 (11%) environmental samples. These were collected from a variety of items in all 4 zones. WGS and AFST revealed that although isolates were similar throughout the country, isolates from the northern region were genetically distinct and more resistant to amphotericin B (AmB) than the isolates from central Colombia. Four novel nonsynonymous mutations were found to be significantly associated with AmB resistance. Conclusions: Our results show that extensive C. auris contamination can occur and highlight the importance of adherence to appropriate infection control practices and disinfection strategies. Observed genetic diversity supports healthcare transmission and a recent expansion of C. auris within Colombia with divergent AmB susceptibility.COL00009627 páginasapplication/pdfengOxford University PressChicago, Estados Unidoshttp://creativecommons.org/licenses/by-nc-nd/2.5/co/https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Molecular Epidemiology of Candida auris in Colombia Reveals a Highly Related, Countrywide Colonization With Regional Patterns in Amphotericin B ResistanceArtículo de investigaciónhttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAnfotericina BAmphotericin BFarmacologíaPharmacologyAgentes AntifúngicosAntifungal AgentsCandidaCandidaCandidiasisCandidiasisEpidemiologíaEpidemiologyFarmacorresistencia FúngicaDrug Resistance, FungalMicrobiología AmbientalEnvironmental MicrobiologyPruebas de Sensibilidad MicrobianaMicrobial Sensitivity TestsEpidemiología MolecularMolecular EpidemiologyTipificación MolecularMolecular TypingTécnicas de Tipificación MicológicaMycological Typing TechniquesSecuenciación Completa del GenomaWhole Genome Sequencinghttps://id.nlm.nih.gov/mesh/D000666https://id.nlm.nih.gov/mesh/D010600https://id.nlm.nih.gov/mesh/D000935https://id.nlm.nih.gov/mesh/D002175https://id.nlm.nih.gov/mesh/D002177https://id.nlm.nih.gov/mesh/D004813https://id.nlm.nih.gov/mesh/D025141https://id.nlm.nih.gov/mesh/D004783https://id.nlm.nih.gov/mesh/D008826https://id.nlm.nih.gov/mesh/D017720https://id.nlm.nih.gov/mesh/D058889https://id.nlm.nih.gov/mesh/D016533https://id.nlm.nih.gov/mesh/D000073336Clin. Infect. Dis.2111568Clinical Infectious DiseasesPublicationORIGINALMisasElizabeth_2018_Molecular_Epidemiology_Candida_auris.pdfMisasElizabeth_2018_Molecular_Epidemiology_Candida_auris.pdfArtículo de investigaciónapplication/pdf2846750https://bibliotecadigital.udea.edu.co/bitstreams/52f79abf-a037-4f6f-a7c6-c455f3743571/download9a30edb9d33f6570d97ffe8cef412c88MD51trueAnonymousREADCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8823https://bibliotecadigital.udea.edu.co/bitstreams/397883d4-1672-40d7-a20c-7f7113f303fc/downloadb88b088d9957e670ce3b3fbe2eedbc13MD52falseAnonymousREADLICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://bibliotecadigital.udea.edu.co/bitstreams/1ad55e44-84b8-4097-ac8f-4c784980a688/download8a4605be74aa9ea9d79846c1fba20a33MD53falseAnonymousREADTEXTMisasElizabeth_2018_Molecular_Epidemiology_Candida_auris.pdf.txtMisasElizabeth_2018_Molecular_Epidemiology_Candida_auris.pdf.txtExtracted texttext/plain35601https://bibliotecadigital.udea.edu.co/bitstreams/b0fc568c-af4c-4eb8-af27-847c6a6eea3e/downloadb8804eae3e680a114d2fb7a09a884458MD54falseAnonymousREADTHUMBNAILMisasElizabeth_2018_Molecular_Epidemiology_Candida_auris.pdf.jpgMisasElizabeth_2018_Molecular_Epidemiology_Candida_auris.pdf.jpgGenerated Thumbnailimage/jpeg17500https://bibliotecadigital.udea.edu.co/bitstreams/53a41756-6dac-4f5a-ac6d-9d26538f114d/download6025f8aade7cc4cd84aa75c3aabd9636MD55falseAnonymousREAD10495/39582oai:bibliotecadigital.udea.edu.co:10495/395822025-03-26 23:52:16.539http://creativecommons.org/licenses/by-nc-nd/2.5/co/open.accesshttps://bibliotecadigital.udea.edu.coRepositorio Institucional de la Universidad de Antioquiaaplicacionbibliotecadigitalbiblioteca@udea.edu.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